Linked Life Data

15466404

Source:http://linkedlifedata.com/resource/pubmed/id/15466404

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-10-6
pubmed:abstractText
The tubulin-binding agent combretastatin A-4-phosphate (CA-4-P), rapidly disrupts the vascular network of tumors leading to secondary tumor cell death. In vitro, CA-4-P destabilizes microtubules and causes endothelial cell death. In this study we analyze the mechanisms by which CA-4-P induces the death of proliferating endothelial cells. We demonstrate that at >/=7.5 nmol/L, CA-4-P damages mitotic spindles, arrests cells at metaphase, and leads to the death of mitotic cells with characteristic G(2)/M DNA content. Mitotic arrest was associated with elevated levels of cyclin B1 protein and p34(cdc2) activity. Inhibition of p34(cdc2) activity by purvalanol A caused mitotic-arrested cells to rapidly exit mitosis, suggesting that sustained p34(cdc2) activity was responsible for metaphase arrest. Pharmacological prevention of entry into mitosis protected cells from undergoing cell death, further establishing the link between mitosis and cell death induction by CA-4-P. CA-4-P-mediated cell death shared characteristics of apoptosis but was independent of caspase activation suggesting the involvement of a non-caspase pathway(s). These data suggest that induction of apoptosis in endothelial cells by CA-4-P is associated with prolonged mitotic arrest. Therefore, by activating cell death pathways, CA-4-P, in addition to being an effective anti-vascular agent, may also interfere with regrowth of blood vessels in the tumor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0002-9440
pubmed:author
pubmed:issnType
Print
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1401-11
pubmed:dateRevised
2011-11-8
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The tubulin-binding agent combretastatin A-4-phosphate arrests endothelial cells in mitosis and induces mitotic cell death.
pubmed:affiliation
Tumour Microcirculation Group, Gray Cancer Institute, PO Box 100, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, UK. kanthou@gci.ac.uk.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't